Characterizing, Understanding and Exploiting lipid-lipid interactions

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Lipids are amphiphilic molecules that play a pivotal role in several biological processes and possess a great potential for the fabrication of nanocarriers. Our research program aims at gaining a better understanding and control of the structures and functions of lipid self-assemblies, investigating 3 specific systems. First, some peptides and proteins can induce lipid efflux from cell membranes, a phenomenon that plays a critical role in sperm maturation and in cholesterol transport. Despite their prime importance, we lack an underlying molecular description of the mechanism of these lipid extractions. We will characterize peptide- or protein-induced lipid extraction of some key systems with an overall approach, from the lipid/protein-peptide association to the resulting mixed complexes. We will particularly examine the chemical and physical features dictating the extraction of specific lipids. Second, the lipids of the stratum corneum (the top layer of the epidermis) are largely responsible for skin impermeability, a property that is proposed to be linked to the unusual crystalline phase they form. We will examine the molecular origin of the formation of solid phases, characterizing the phase behavior of different model mixtures and determine the correlation between the crystalline phases and the impermeability of the SC lipid models. The resulting improved knowledge will contribute to maintaining a healthy skin barrier, and potentially to altering the barrier for transdermal drug delivery. Third, my group is developing a novel family of liposomes formed with a monoalkylated amphiphile and a sterol. These liposomes display some distinct properties including a very low permeability. We propose to push further the development of these novel nanovectors by creating non phospholipid liposomes with specific properties: e.g. stealth liposomes that have an interesting potential for intravenous drug delivery, liposomes with alkylated sugar group to create new nanocarriers with a potential for targeted drug delivery, and light-sensitive liposomes. We believe that the combination of the exceptional impermeability and controlled release response grants an interesting potential for these non phospholipid cholesterol-rich liposomes.